Acetic Acid → HCID 178483062, compound

HRID 1984885Notes

Reaction equation

HRID 1984885 reaction equation
[NH2:1][CH2:2][C@H:3]1[CH2:8][CH2:7][C@H:6]([CH2:9][NH:10][C:11]2[N:20]=[C:19]([N:21]([CH3:23])[CH3:22])[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[N:12]=2)[CH2:5][CH2:4]1.[Br:24][C:25]1[CH:32]=[CH:31][C:28]([CH:29]=O)=[C:27]([O:33][C:34]([F:37])([F:36])[F:35])[CH:26]=1.C(O)(=O)C.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>C(Cl)Cl>[Br:24][C:25]1[CH:32]=[CH:31][C:28]([CH2:29][NH:1][CH2:2][C@H:3]2[CH2:8][CH2:7][C@H:6]([CH2:9][NH:10][C:11]3[N:20]=[C:19]([N:21]([CH3:23])[CH3:22])[C:18]4[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=4)[N:12]=3)[CH2:5][CH2:4]2)=[C:27]([O:33][C:34]([F:35])([F:36])[F:37])[CH:26]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 5049666Sodium triacetoxyborohydrideHCID 187000874-Bromo-2-(trifluoromethoxy)benzaldehydeHCID 178483061HCID 178483061, compound

Product 1

HCID 178483062HCID 178483062, compoundYield 89%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of trans-N2-(4-aminomethyl-cyclohexylmethyl)-N4,N4-dimethyl-quinazoline-2,4-diamine (500 mg, 1.59 mmol) in CH2Cl2 (5 mL) were added 4-bromo-2-trifluoromethoxy-benzaldehyde obtained in step A of example 13 (428 mg, 1.59 mmol), acetic acid (95 mg, 1.59 mmol), and NaBH(OAc)3 (505 mg, 2.38 mmol). The reaction mixture was stirred at ambient temperature for 4 hr. The reaction was quenched with saturated aqueous NaHCO3. The aqueous layer was extracted with CHCl3 (three times). The combined organic layer was dried over MgSO4, filtered, concentrated, and purified by flash chromatography (NH-silica gel, 50% EtOAc in hexane) to give trans-N2-{4-[(4-bromo-2-trifluoromethoxy-benzylamino)-methyl]-cyclohexylmethyl}-N4,N4-dimethyl-quinazoline-2,4-diamine (783 mg, 89%) as a pale yellow solid.

Workup

  1. customThe reaction was quenched with saturated aqueous NaHCO3
  2. extractionThe aqueous layer was extracted with CHCl3 (three times)
  3. dry with materialThe combined organic layer was dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. custompurified by flash chromatography (NH-silica gel, 50% EtOAc in hexane)

Sources & evidence

ORD record
ord-411019c2e1194a04b1c1735bdabe3549
Source dataset
uspto-grants-2009_06
Patent number
US07544690B2

Reaction notes

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